Ocular delivery of macromolecules

Abstract

Biopharmaceuticals are making increasing impact on medicine, including treatment of indications in the eye. Macromolecular drugs are typically given by physician-administered invasive delivery methods, because non--invasive ocular delivery methods, such as eye drops, and systemic delivery, have low bioavailability and/or poor ocular targeting. There is a need to improve delivery of biopharmaceuticals to enable less-invasive delivery routes, less-frequent dosing through controlled-release drug delivery and improved drug targeting within the eye to increase efficacy and reduce side effects. This review discusses the barriers to drug delivery via various ophthalmic routes of administration in the context of macromolecule delivery and discusses efforts to develop controlled-release systems for delivery of biopharmaceuticals to the eye. The growing number of macromolecular therapies in the eye needs improved drug delivery methods that increase drug efficacy, safety and patient compliance.

Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications

“…Limited diffusion across the cornea and the increased washing through the tear drainage result in a low bioavailability of 1-7% for most approved drugs [26]. New administration routes, and ideally a controlled-release drug delivery through biodegradable polymeric implants [27], would lead to increased success rates of corneal transplantation in these severe inflamed corneas.…”

Visual tracing of diffusion and biodistribution for amphiphilic cationic nanoparticles using photoacoustic imaging after ex vivo intravitreal injections

“…1,2 To treat these disorders, most drugs need sustained and effective delivery to the posterior segment of the eye. 3 This part of the eye is composed of a blood-retinal barrier and an inner retinal limiting membrane that are relatively impermeable to many therapeutic agents.…”

Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma

“…First, forming a drug depot adjacent to the ciliary body enabled dose sparing, which is not only of interest to reduce side effects, but also enables a smaller injection to contain enough drug for a longer duration of effect. Second, the supraciliary space is not in the visual axis and therefore should not affect vision the way eye drops or intravitreal injections can [62,63]. …”